ACR Puts Out Gout Guidelines

Action Points

The American College of Rheumatology (ACR) has issued new guidelines for the management of gout that reflect the broadening range of therapeutic options, greater awareness of the need for urate control, and the increasing burden and prevalence of this disease.

Note that either of the xanthine oxidase inhibitors, allopurinol or the newer agent febuxostat, can be used as a first-line urate-lowering therapy, and the target serum urate levels should be below 6 mg/dL.

The American College of Rheumatology (ACR) has issued new guidelines for the management of gout that are intended to reflect the broadening range of therapeutic options, greater awareness of the need for urate control, and the increasing burden and prevalence of this disease.

For instance, either of the xanthine oxidase inhibitors, allopurinol or the newer agent febuxostat (Uloric), can be used as a first-line urate-lowering therapy, according to Robert Terkeltaub, MD, of the University of California San Diego, and colleagues.

Furthermore, the target serum urate levels should be below 6 mg/dL, and in many patients may need to be below 5 mg/dL, their task force reported in the October issue of Arthritis Care & Research.

"Long-term morbidity and impairment of health-related quality of life are now better appreciated in many gout patients, particularly those with multiple comorbidities and/or chronic gouty arthritis," the authors wrote.

Initial measures should include patient education about the role of uric acid in the disease, and nonpharmacologic approaches such as limiting intake of purine-rich meat and seafood, as well as alcohol, they explained.

But in the majority of patients, lifestyle efforts are unlikely to suffice and pharmacotherapy will need to be instituted.

An important aspect of initial treatment decision-making, according to the task force, must be identification of patient comorbidities such as kidney disease and cardiovascular conditions, along with recognition of drug interactions and the use of medications such as thiazide diuretics that can influence serum urate levels.

Allopurinol is the most commonly used urate lowering agent, but flares often occur early in treatment that can interfere with adherence, so the task force emphasized that the initial dosage should not exceed 100 mg per day, or 50 mg per day for patients with advanced chronic kidney disease.

This dose should be titrated upwards, typically to 300 mg per day, but higher doses can be used if the urate remains high and the patient is monitored for hypersensitivity.

Another recommendation was that patients who are of Korean, Han Chinese, or Thai origin be screened for the HLA-B*5801 allele, which confers a very high risk for allopurinol sensitivity.

If the initial agent chosen is febuxostat, the highest FDA approved dose is 80 mg per day, but the ACR task force noted that in other countries, doses up to 120 mg are used and may be tried if needed.

If the target serum urate level cannot be achieved with the xanthine oxidase inhibitors, a uricosuric agent such as probenecid (Benemid), fenofibrate, or losartan (Cozaar) can be added, but more work will be needed to determine the optimal combination approach.

"The authors believe that ongoing and further studies will help understand how to optimize combinations of uricosuric agents with [xanthine oxidase inhibitor] therapy to decrease the risk of uricosuric-induced urolithiasis, while increasing the velocity of size reduction of body urate stores and tophi," they wrote.

If that approach is inadequate or the patient is intolerant, pegloticase (Krystexxa) can be used for severe disease, although the duration of treatment with this agent remains uncertain.

The authors noted their recommendations do not take into account cost of treatment, so physicians will need to consider this in conjunction with patient preferences and long-term safety.

"Importantly, societal cost of healthcare and cost and cost-effectiveness differences between therapies are excluded from analysis by the RAND/UCLA Appropriateness Method" used in developing these recommendations, they stated.

The guidelines also addressed the treatment of the acute attack, emphasizing that any attack should be treated pharmacologically, preferably beginning within 24 hours of symptom onset, while urate-lowering therapy continues.

Several options are available depending on symptom severity, usually with monotherapy as the initial approach.

For mild-to-moderate symptoms in a few joints, oral nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, or systemic corticosteroids can be tried.

"It is at the discretion of the prescribing physicians to choose the most appropriate monotherapy based on the patient's preference, prior response to pharmacologic therapy for an acute gout attack, and associated comorbidities," the authors advised.

Colchicine is an additional recommended first-line treatment for the acute attack, but must be initiated within 36 hours of symptom onset, they cautioned.

Treatment with colchicine typically begins with a loading dose of 1.2 mg, followed by a second 0.6 mg dose an hour later, and then once or twice per day until symptoms resolve.

But if pain is severe and multiple or large joints are affected, combination therapy may be appropriate, using colchicine and NSAIDs, oral steroids and colchicine, or these drugs plus intra-articular steroid injections.

The authors further recommended that for patients with ongoing disease activity after the acute symptoms resolve, consideration be given for anti-inflammatory prophylaxis using lower doses of colchicine or NSAIDs, possibly for 3 to 6 months after the target urate level is reached.

The panel did not recommend a specific NSAID, noting that the FDA has approved naproxen, indomethacin, and sulindac for gout attacks, but others may also be effective.

They did not advise the use of complementary or alternative therapies for acute flares.

Ongoing research also will be needed to determine the role of advanced imaging techniques such as high resolution ultrasound and dual-energy CT for assessment of disease status and response to treatment.

"It is hoped that publication of these guidelines, along with effective patient education in gout treatments and the objectives and safety issues of management, will improve patient adherence, quality of care, and outcomes in management of gout," they concluded.

The authors noted that a limitation of the recommendations are that only about one-third were based on the highest (A) level of evidence -- signifying evidence from more than one clinical trial -- and that half were level C -- derived from expert opinion or case studies.

Therefore, more studies will be needed to fully develop the optimal treatment approaches for prophylaxis and treatment.

The study was supported by the ACR and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.